Purpose <p>Blood-brain barrier disruption (BBBD) strategies for treating high-grade gliomas (HGGs) have advanced rapidly, yet consensus regarding clinical efficacy remains lacking. A comprehensive review of BBBD methods is needed to consolidate outcomes and guide clinical adoption and research.</p> Methods <p>A scoping review following PRISMA-ScR guidelines was performed to identify studies reporting methods and efficacy outcomes of BBBD for HGG. PubMed, Embase, Scopus, and Web of Science were systematically searched. Clinical studies testing any BBBD method in adult HGG were included if they reported at least one predefined efficacy endpoint: median overall or progression-free survival, brain drug concentration, or radiographic response. Neurological adverse events (AEs) attributed to BBBD were recorded.</p> Results <p>Thirty-seven studies (498 participants) met inclusion criteria and evaluated intra-arterial hyperosmolar mannitol, ultrasound with microbubbles, laser interstitial thermal therapy, liposomal encapsulation, or regadenoson. Seven ultrasound studies reported pharmacokinetic evidence of increased drug delivery, with brain drug concentration increases ranging from 2 to 5.93-fold. Radiographic responses were variably reported and were not comparable across modalities. Survival outcomes were primarily reported in single-arm studies, and use of comparator arms was limited to nonrandomized or historical controls. Seizure was the most common BBBD-associated AE, particularly with intra-arterial hyperosmolar mannitol (55/146, 37.7%).</p> Conclusions <p>BBBD represents a promising strategy for HGG treatment, with pharmacokinetic evidence of increased brain drug delivery and exploratory survival data reported in early trials. Although high-grade AEs were uncommon, seizures were prevalent in hyperosmolar mannitol studies. Prospective randomized controlled trials incorporating modern molecular classification are needed to define future clinical applications.</p> Clinical trial number <p>Not applicable.</p>